Process of preparing (beta halo alkoxy) benzoic acid



2,696,498 Patented Dec. 7, 1954 United States Patent Ofiice wherein Xrepresents C1 or Br, and y and R are as 2,695,493 defined above.

PROCESS OF PREPARING ('3 HALO ALKOXY) The details of the presentinvention will be apparent BENZOIC ACID 5 from a consideration of thefollowing specific example:

Paul Edward Hoch, Easton, and George Wesley Pedlow, Jr., Lock Haven,Pa., and Robert Lee Sundherg, Alpha, N. J., assignors to General Aniline& Film Corporation, New York, N. Y., a corporation of DelawarePreparation of (fi-hydroxyethoxy) benzoic acid To a mixture of 310.5 g.salicylic acid, 1.55 g. sodium hydroxide and 100 g. chlorobenzene wasadded 222 g. gaseous ethylene oxide at a pressure of -32 lb. p. s. i. g.over a period of 4 hours with good stirring at a temperature of 120-130C. There was obtained a total 15 of 623.4 g. of product. Assuming theonly weight losses are due to escape of ethylene oxide, the mole ratioof No Drawing. Application February 7, 1951, Serial No. 209,918

6 Claims. (Cl. 260-521) This invention relates to novel (,3-hydroxy-, orfi-haloethoxy) benzoic acids and their acid halides and a ethylene oxideto salicylic acid was 2 method of preparing the same.

It has been found that valuable fluorescent compounds gIZamS the thusobtfined ethoxylated Salicylic can be obtained by condensing an acidhalide, usually 0 and reaction mixture was stirred at reduced pressurethe acid chlorlde of (fi-haloethpxy) ethyl benzoic acid while heating onthe steam bath to remove chlorobenzene wlth a dlammo stllbenedlsulfomc(Particularly 414' solvent. 522 grams of solvent-free product wasobtained. diamino 2,2 stilbene disulfonic acid). However, such 700 1 f 39 N h d 273 l B-halo ethoxy)benzoic acids and their acid chlorides 0 m yrox e mo es have not heretofore been available. 2 w ded. and thercsultmg mlxture Was heated It has now been found that these productsmay readily Y on the steam bath 4% hours'. The mixture was allowed beProduced the followmg manner: to cool to C. and 145 g. conc. H2804 inapproxi- (fi-hydroxy ethoxy, or propoxy) benzoic acid is prepared byreacting a hydroxy benzoic acid With 2 or more mately 150 Ice was addedat a rate to keep tempera molar proportions of ethylene or propyleneoxide in the 30 ture from exiieeding The mixture was trans presence ofan alkaline catalyst to yield B-hydroxyethyl, I ferred to a separatoryfunnel and 300 ml. methylene T 5'hydr0xypr0pyl, (fi' ethoxy P P chloridewas added. The mixture was shaken well and benzoate which is thensaponified and the saponified product is then acidified to obtain the(fl-hydroxyethoxy, then allowed to separate The lower layer was drawn orp-hydroxypropoxy) benzoic acid. These reactions 35 0E and Washed threetimes (each time with about 1/3 proceed as illustrated in the followingequation: to /2 its volume of water). The. lower methylene wherein x andy are small integers of from 1 to 3 and having an average value slightlyabove 1, preferably about 1.1 and one of the Rs is H and the other 55 Ris H or methyl.

The (fi-haloethoxy, or B-halopropoxy) benzoyl halide chloride layer wasthen placed in a flask equipped with a water separator and the mixturerefluxed until little, if any, water appeared to be coming off. Theflask .mixture was allowed to cool and 150 g. anhydrous sodium may thenbe prepared by treating th thu bt i d sulfate added. After mixing welland allowing to stand (fi-hydroxyethoxy or propoxy) benzoic acid with anfor a short time, the drying agent was filtered OE and @Xcess 0f thionylchloride, or bromide. or Phosphorus 6 the process repeated with anadditional 150 g. of anhypentachloride, or bromides, in order to produce(fi-chloro, drous o, (and filtered). The filtrate was placed in or bromoethoxy or propoxy) benzoyl chlonde or a flask and the methylene chloridedistilled ofl at reduced {$5 33%; 1 312 gg i g g gggsg 12 $12 2 3:pressure (20-25 mm.) not allowing the temperature to or bromo ethoxbenzoic acid. These reactions ma be exceed illustrated by fi t efollowing equation: y 60 g. of activated charcoal (Norite) was added tothe COOH COOH

resulting oil and the mixture stirred for a short time a t roomtemperature. The charcoal was filtered ofl by suction. Yield 350 g.(855% of theory.)

It is probable that the product, obtained, as above described,-:contained, in addition to the ti-hydroxyethoxy benzoic acid, aismall-amount of product having .a poly- ,glycol ether radica1, -i. .e.,compounds in which y in the equation given above was greater than one.'It is also possible that a 'small amount of 'low polymer (polyester) ofthe following 'type was present O CHzCHsO However, it has been foundthat such polymeric products need not ,be separated. 'The productpurified 'to the extent indicated is satisfactory for use, forconversion into B-c'hloroethoxy benzoyl chloride which in (turn,probably contain products :having a polyglycol ether group butaresuitable ,for use. in .the .form :in which they are obtained asdescribed below.

In the reaction of the salicyclic acid with ethylene oxide, it isdesirable to carry out the reaction under conditions at which theethylene oxide, (or propylene oxide if it should be used), reactsprimarily only with the carboxyl and phenolic hydroxy groups of thehydroxy benzoic acid and reacts to a minor extent, if at all, with thealiphatic hydroxyls formed.v Therefore, preferably only a slight excessof the amount of ethylene or propylene oxide is used-about 2.15 to 2.25moles per mole of hydroxy benzoic acid and reaction is mostadvantageously carried out at a temperature of about 130 C. and in thepresence of an inert solvent such as chlorobenzene, although other inertsolvents may be used, if desired.

It is probable that the product formed in the reaction of-ethylene .(orpropylene) oxideand the hydroxy benzoic .acid is a mixture of estersincluding dimers, trimers and low polymers. By saponificafion of thisreaction product, the sodium salt of desired (fi-hydroxy-ethoxy) benzoicacid is obtained and all polymeric products are hydrolyzed to monomers.After acidification of the sodium salt,'.the product -"(iree acid) "isadvantageously dried in the presence of an appropriate solvent suchas-methylene chloride. During this drying, it :is important that thetemperature be kept low and that suflicient dilution is obtained by theuse of methylene chloride (or similar water insoluble solvent for thefree acids) so that the free carboxyl groups will not react appreciablywith the hydroxy groups-available. The free acids are soluble in themethylene chloride and therefore much water, glycols and inorganic salts(formed by neutralization) are conveniently removed due to theirinsolubility in methylene chloride. As examples of other appropriatesolvents for use in place of methylene chloride, there may be mentionedsuch solvents as ethylene chloride, benzene, pentane, hexane, heptane,toluene, xylene and other higher boiling solvents may be usedconveniently if water removal and solvent removal is carried out atreduced pressure to keep temperature low and thus prevent polymerizationto the polyester type of polymer previously shown.

Preparation of 2(B-chlor0eth0xy) benzoyl chloride To 36.4 g. (0.2 mole)of 2-;8-hydroxyethoxy benzoic acid prepared as above described was addedslowly 150 cc. of thionyl chloride. After the initial reaction ceased,

'to stand overnight at room temperature.

4 the solution was refluxed for three hours and permitted After removalof the excess thionyl chloride, the acid chloride was distilled invacuo. The product Z-(B-chloroethoxy) benzoyl chloride was colorlessliquid B. P. 144-147/ 3 mm. which solidified on standing. Yield '20 g.

The-thus obtained Mil-chloroethoxy) benzoyl chloride may "be hydrolyzedto the (free acid by refluxing with water or by merely allowing "tostand in contact with water.

t .It will be apparent that in place of salicylic acid there may beusedmeta or para hydroxy benzoic acids in order to obtain productscontaining the (3-hydroxyethoxy group or the B-chloroethoxy group inmeta or para position, respectively, the other conditions of reactionremaining substantially the same. Thus, by using m-hydroxybenzoic acidin place of salicylic acid in the above described synthesis there isobtained 3(B-hydroxyethoxy) benzoic acid and 3'(sfi-chloroethoxyjb'enzoyl chloride com 00 CHfCHrCl and 4(,Chl0roethoxy)benzoyl chloride O CHz-CHtCl We claim:

.1. The method of producing (ti-halo alkoxy) benzoic acid whichcomprises reacting at a temperature of about C. a hydroxy benzoic acidwith an alkylene oxide selected from the group consisting of ethyleneand propylene .oxidein a molar ratio of about 1:2 in an inert solventand in the presence of an alkaline alkylene oxide condensation catalystto thereby produce a 3 hydroxy alkyl ([3 vhydroxyalkoxy) benzoate,saponifying the thus obtained ester to convert it to an alkali salt of(p hydroxyalkoxy) benzoic acid, acidifying at about 40 "C. the thusformed salt to convert it to the corresponding acid, mixing the thusacidified product with an inert solvent for the beta-hydroxyalkoxybenzoic acid and drying the same at a temperature below 45 C. treatingthe thus obtained (5 hydroxyalkoxy) benzoic acid with an excess of ahalogenating agent selected from the group consisting of thionylchloride and bromide and "phosphorus penta'chloride and bromide, wherebythere is formed a (e haloalkoxy) benzoic acid halide, and hydrolyzingthe thus obtained acid chloride whereby there is formed a (B haloalkoxy)benzoic acid and recovering the same.

2. The processs as defined in claim 1 wherein the alkylene oxideemployed is ethylene oxide whereby there is formed and recovered a (,8haloethoxy) benzoic acid.

-3. The process as defined in claim 2 wherein the halogenating agentspecified is thionyl chloride whereby acid halides which comprisesreacting at a temperature of about 130 C. a hydroxy benzoic acid with analkylene oxide selected from the group consisting of ethylene andpropylene oxide in a molar ratio of about 1:2 in an inert solvent and inthe presence of an alkaline alkylene oxide condensation catalyst tothereby produce a p-hydroxy alkyl (5 hydroxyalkoxy) benzoate,saponifying the thus obtained ester to convert it to an alkali salt of(B hydroxyalkoxy) benzoic acid, acidifying atabout 40 C. the thus formedsalt to convert it to the corresponding acid, mixing the thus acidifiedproduct with an inert solvent for the beta-hydroxyalkoxy benzoic acidand drying the same at a temperature below 45 C. treating the thusobtained (fl-hydroxyalkoxy) benzoic acid with an excess of ahalogenating agent selected from the group consisting of thionylchloride and bromide and phosphorus pentachloride and bromide, wherebythere is formed a (13 haloalkoxy) benzoic acid halide.

5. The process as defined in claim 4 wherein the alkylene oxide employedis ethylene oxide whereby there is obtained a (fi-haloalkoxy)-benzoicacid halide.

6. The process as defined in claim 5 wherein the 6 halogenating agentspecified is thionyl chloride whereby there is obtained a(p-chloroethoxy) benzoic acid chloride.

References Cited in the file of this patent UNITED STATES PATENTS NumberName Date 2,113,374 Hall Apr. 5, 1938 2,531,502 De Groote Nov. 28, 1950FOREIGN PATENTS Number Country Date 213,593 Germany Sept. 14, 1909412,699 Germany Apr. 25, 1925 470,181 Great Britain Aug. 3, 1937 Smith,J. Am. Chem. 800., vol. 62, p. 994 (1940).

1. THE METHOD OF PRODUCING (B-HALO ALKOXY) BENZOIC ACID WHICH COMPRISESREACTING AT A TERMPERATURE OF ABOUT 130* C. A HYDROXY BENZOIC ACID WITHAN ALKYLENE OXIDE SELECTED FROM THE GROUP CONSISTING OF ETHYLENE ANDPROPYLENE OXIDE IN A MOLAR RATIO OF ABOUT 1:2 IN AN INERT SOLVENT AND INTHE PRESENCE OF AN ALKALINE ALKYLENE OXIDE CONDENSATION CATALYST TOTHEREBY PRODUCE A B HYDROXY ALKYL (B HYDROXYALKOXY) BENZOATE,SAPONFIYING THE THUS OBTAINED ESTER TO CONVERT IT TO AN ALKALI SALT OF(B-HYDROXYALKOXY) BENZOIC ACID, ACIDIFYING AT ABOUT 40* C. THE THUSFORMED SALT TO CONVERT IT TO THE CORRESPONDING ACID, MIXING THE THUSACIDIFIED PRODUCT WITH AN INERT SOLVENT FOR THE BETA-HYDROXYALKOXYBANZOIC ACID AND DRYING THE SAME AT A TEMPERATURE BELOW 45* C. TREATINGTHE THUS OBTAINED (B HYDROXYALKOXY) BANZOIC ACID WITH AN EXCESS OF AHALOGENATING AGENT SELECTED FROM THE GROUP CONSISTING OF THIONYLCHLORIDE AND BROMIDE AND PHOSPHORUS PENTACHLORIDE AND BROMICE, WHEREBYTHERE IS FORMED A (B HALOALKOXY) BENZOIC ACID HALIDE, AND HYDROLYZINGTHE THUS OBTAINED ACID CHLORIDE WHEREBY THERE IS FORMED A (B HALOALKOXY)BENZOIC ACID AND RECOVERING THE SAME.